[Psychiatrists, HIV-infected patients and compulsion--keep medical therapy and social control apart!].
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Ethics, Medical↗
Biomedical subjects
M Asberg
Publications and source records attributed to M Asberg.
Effects of fluoxetine treatment of platelet 3H-imipramine binding, 5-HT uptake and 5-HT content in major depressive disorder.
Platelet 3H-imipramine binding, serotonin (5-HT) uptake and 5-HT concentrations were studied in 14 hospitalized patients with depressive disorder following 6 weeks of treatment with a selective 5-HT uptake blocker, fluoxetine. After 3 weeks of treatment there was a significant decrease in Bmax of 3H-imipramine binding and a significant increase in Kd. A highly significant decrease in Vmax of 5-HT uptake was seen after 3 weeks of treatment which was accompanied by a slight increase in Km. At the same time the platelet 5-HT content was significantly reduced by about 90% of its original level. The platelet 5-HT content continued to decrease with further treatment while there was a tendency for Vmax to return to pretreatment levels. The affinity of the 5-HT uptake carrier continued to decrease significantly. There was no further significant change in Bmax of 3H-imipramine binding during further treatment, although there was an increase in Bmax in the majority of patients. The changes in Bmax and Vmax were closely associated throughout the treatment. In some cases the changes in different platelet parameters correlated with the changes in depression rating scores during treatment, but this correlation did not reach statistical significance.
Adult↗
Violent and nonviolent suicide attempts--a controlled Rorschach study.
Rorschach records from 20 patients who had made active, violent suicide attempts were compared with records from 20 patients who had taken drug overdoses and 20 psychiatric control patients who had not made a suicide attempt. Ego function ratings showed that violent attempters were more paranoid than both other groups and less able to cope with conflict situations, to handle dysphoric affect and to differentiate between reality and imagination. Violent attempters had lower level of cognitive maturity than controls and tended to produce fabulized combination responses, suggesting cognitive slippage, and distorted human content responses, indicating pathological object relationships. Nonviolent attempters did not differ from controls. Six patients, all from the violent attempt group, completed suicide within a follow-up period of 4 years. Compared with the survivors, they were less tolerant of dysphoric affect and showed more pronounced decline of developmental level within cards. Completers could be identified on the Rorschach at 55% sensitivity and 93% specificity.
Adult↗
Suicidal behavior and cognitive flexibility: design and verbal fluency after attempted suicide.
Aspects of problem solving were measured in nine male psychiatric patients, hospitalized after attempted suicide. Testing took place within 3 weeks (except for one patient) of the suicide attempt. Controls were patients with chronic idiopathic pain and healthy volunteers. Suicidal patients had significantly lower scores on general intellectual tests and in verbal and design fluency. No differences in problem solving (the Perceptual Maze Test and the Wisconsin Card-Sorting Test) and flexibility (the Uses of Objects Test and the Stroop Test) were found. The results are interpreted as indicating a decreased ability of suicidal patients to generate new ideas, when no alternatives are provided.
Adolescent↗
Biochemical aspects of suicidal behavior.
1. In completed suicides, studies of brain regions and CSF indicate a dysfunction of the serotonergic system. 2. In suicidal patients, regardless of diagnoses, analyses of monoamine metabolites in lumbar CSF reveal decreased concentrations of the serotonin metabolite 5-HIAA. 3. In depressed suicidal patients, both low CSF 5-HIAA and low concentrations of the dopamine metabolite HVA are associated with suicidality. In addition, pathological dexamethasone-tests may indicate an increased suicide-risk in these patients. 4. In depressed patients, there is evidence that the association between CSF 5-HIAA and corticosteroids is in contrast to findings in depressed suicidal patients.
Adrenal Cortex Hormones↗
Effects of antidepressant treatments on platelet tritiated imipramine binding in major depressive disorder.
The effects of four antidepressant treatments on platelet tritiated imipramine binding have been studied in 51 hospitalized patients with severe major depressive disorder. There was an increase in maximum binding (Bmax) during the first week of treatment with antidepressants and electroconvulsive therapy, which was further magnified after three weeks' treatment with the serotonin uptake blockers alaproclate and zimeldine hydrochloride, but the Bmax values returned to baseline levels with nortriptyline hydrochloride and electroconvulsive therapy. The equilibrium dissociation affinity constant (Kd) did not change with any of the treatments. On reexamination one or two years after admission to the study, Bmax had not reached control values in clinically recovered, drug-free patients. Low pretreatment Bmax was associated with delusions during illness and with a poor long-term clinical outcome. There was no correlation between binding parameters and monoamine metabolite concentrations in the cerebrospinal fluid, either before or during treatment.
Adult↗
Neuropsychological correlates of platelet monoamine oxidase (MAO) activity in female and male subjects.
Platelet monoamine oxidase (MAO) activity has been found to have behavioral (psychiatric and personality) correlates and is assumed to be linked to central transmitter systems and thus presumably to neuropsychological processes. In the present study, computerized neuropsychological tests, a reaction time (RT) test and a visuo-spatial problem solving test, the Perceptual Maze Test (PMT), were given to 32 female and 29 male students, each sex group divided into three subgroups on the basis of platelet MAO activity. The tests yield measures of laterality (reaction time for left- versus right-sided stimuli) and different aspects of cognitive strategy and skill, e.g. time used for inspection of the maze, for processing the stimulus pattern, and for checking the correctness of solutions. Low MAO female subjects had shorter RTs, pronounced for left-sided stimuli, and shorter inspection times in the PMT compared to other female subjects. Low and high MAO males had difficulties in inhibiting responses, when required, and low MAO males were more rapidly prepared to respond to new stimuli after short intervals than other males. In the PMT, high MAO male subjects spent a smaller part of the total time on inspection in relation to other male groups and had more rubouts than low MAO males, whose maze solving behavior indicated higher visuo-spatial ability. The results are discussed in terms of possible neurochemical bases of impulsivity and psychopathy, and of spatial skill.
Adolescent↗
Markers for vulnerability to psychopathology: temperament traits associated with platelet MAO activity.
The functional linkage between platelet MAO activity and psychopathology was explored by analyzing temperamental correlates in 40 male subjects by means of scales from the Eysenck Personality Questionnaire (EPQ), the Zuckerman Sensation Seeking Inventory, and the Karolinska Scales of Personality (KSP). Linear correlations were found with two sensation seeking scales, replicating earlier findings. However, nonlinear correlations predominated. Subjects with intermediate platelet MAO activity had higher scores in conformity scales and lower scores in anxiety and hostility scales than low and high MAO subgroups. Low MAO subjects showed a pattern of higher scores in KSP Impulsiveness, EPQ Neuroticism, and KSP Somatic Anxiety and Irritability and lower scores in KSP Socialization, in line with personality profiles found in alcoholics, psychopaths, and suicide attempters who also tend to have low platelet MAO activity. High MAO subjects scored lower in sensation seeking and conformity scales and higher in KSP Psychasthenia, Muscular Tension and Suspicion scales, consistent with clinical links between high platelet MAO activity and anxiety and paranoia.
Adult↗
Personality correlates of platelet monoamine oxidase (MAO) activity in female and male subjects.
Associations between platelet monoamine oxidase (MAO) activity and scale scores from the Eysenck Personality Questionnaire, the Impulsiveness-Venturesomeness-Empathy inventory and the Karolinska Scales of Personality were studied in 32 female and 29 male students (age range 17-19 years). There were significant negative correlations between MAO activity and extraversion-related scales for male subjects; in the female group the correlations were also negative but nonsignificant. When comparing subgroups with low, intermediate, and high platelet MAO activity subjects, consistent trends were observed in the direction of higher scores in the impulsivity scales, the sensation seeking-related Monotony avoidance scale, and the Indirect Aggression scale for both female and male low MAO activity groups.
Adolescent↗
Skin conductance habituation and cerebrospinal fluid 5-hydroxyindoleacetic acid in suicidal patients.
The concentration of 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid (CSF) and psychophysiologic variables, such as habituation of the skin conductance response, were measured in 35 drug-free, suicidal inpatients. Twenty-four patients were hospitalized after a suicide attempt, and another 11 had suicidal ideation. The suicide attempters were classified into nonviolent (drug overdoses taken orally, or a single wrist cut) and violent (all other methods). As in previous studies, the suicide attempters had significantly lower CSF concentrations of 5-HIAA compared with healthy, matched controls. The distribution of habituation rate was bimodal (slow and fast habituators). All violent attempters were fast habituators, as were all four patients who in a one-year follow-up were found to have completed a suicide (all by violent methods). The lowest frequency of fast habituators was found in the group of patients with suicidal ideation. There was no correlation between CSF 5-HIAA and habituation rate. A combination of these two variables yielded a highly significant correlation with type of suicide behavior, both retrospectively and prospectively.
Adult↗
Biochemical effects of antidepressant treatment--studies of monoamine metabolites in cerebrospinal fluid and platelet [3H]imipramine binding.
Two putative markers of serotonergic function, the concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) and the binding parameters of [3H]imipramine to blood platelets, are discussed. Pretreatment concentrations of 5-HIAA in the cerebrospinal fluid (CSF) are lower in depressed patients than in normal controls, and a low concentration of the metabolite is associated with an increased risk of suicide. Many studies have attempted to use pretreatment concentrations of 5-HIAA, of the noradrenaline metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) and of the dopamine metabolite homovanillic acid (HVA) as predictors of therapeutic effect. On the whole, HVA appears to predict the effects of diverse treatments rather better than 5-HIAA. Treatment with antidepressant drugs changes the amine metabolite concentrations in the CSF in a relatively predictable way. Thus, administration of selective inhibitors of serotonin uptake has a more profound effect on CSF 5-HIAA, while noradrenaline uptake inhibitors preferentially reduce CSF MHPG concentrations. The Bmax of [3H]imipramine binding to blood platelets has been found to be lower in untreated depressed patients than in healthy controls in several studies. In a study from our group, three weeks' treatment with the serotonin uptake blockers zimeldine and alaproclate increased Bmax, while neither nortriptyline nor electroconvulsive treatment caused any change in Bmax after this time period. One year after initiation of treatment, patients who had clinically recovered and were no longer taking drugs still had a low Bmax of [3H]imipramine platelet binding. Prophylactic lithium caused a significant, but transient decrease in the Bmax of platelet [3H]imipramine binding in euthymic bipolar patients.
Antidepressive Agents↗
Circadian rhythm of serotonin transport in human platelets.
The circadian rhythm of serotonin active transport in human platelets was investigated in ten healthy men, aged 27-35 years. Blood was collected at 08.00, 14.00, 20.00, 02.00 and 08.00 hours the next morning. Simultaneous evaluation of the mean platelet volume, platelet distribution width, platelet distribution skewness and platelet number in whole blood was performed. Km and Vmax for serotonin transport varied considerably among individuals over 24 h. However, the mean values and distribution of these kinetic parameters were reduced at 02.00 hours. All platelet size or number parameters were stable and normal over 24 h; therefore, the reduction in mean Km and Vmax values at 02.00 h is not related to morphological platelet differences but either to platelet intrinsic factors or plasmatic variables. Knowledge of the affinity and capacity of serotonin transport throughout the diurnal cycle is important for future comparisons with depressed patients as well as other hormonal rhythms in patients and healthy humans.
Adult↗
Serotonergic function and suicidal behavior in personality disorders.
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Brain↗
Cerebrospinal fluid studies in suicide. An overview.
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Aggression↗
Therapeutic effects of serotonin uptake inhibitors in depression.
Depression has been associated with a disturbance in serotonin function as reflected in platelet uptake of the transmitter as well as in CSF levels of its major metabolite, 5-hydroxyindoleacetic acid (5-HIAA). CSF 5-HIAA levels are subnormal in approximately 30% of melancholia patients. Early studies suggested that patients with a disturbed serotonin metabolism were less responsive to treatment with uptake inhibitors with a preferential action on noradrenaline neurons. Such findings encouraged the search for compounds with a selective effect on serotonin neurons. Although some classical antidepressants are potent inhibitors of serotonin uptake, they are not selective, since their metabolites, which appear to have antidepressant effects, inhibit noradrenaline uptake. The consistent findings of an increased risk for suicide in patients with low CSF 5-HIAA underlines the importance of exploring drugs that act on serotonin transmission. The biochemical effects of some serotonin uptake inhibitors and their clinical and research potential in depression are reviewed.
5-Hydroxytryptophan↗
Biochemical aspects of suicide.
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Amines↗
Lower 3H-imipramine binding in platelets from untreated depressed patients compared to healthy controls.
3H-Imipramine binding in platelets was measured in 63 severely depressed hospitalized patients, who had been drug free (with the exception of moderate doses of benzodiazepines) for at least 1 month, and in 53 healthy control subjects of comparable age and sex distribution. Bmax of 3H-imipramine binding was significantly lower in the depressed subjects (1012 +/- SD 295 vs. 1123 +/- SD 178 fmole/mg protein). Depressed patients who had attempted suicide by violent means tended to have higher Bmax than nonviolent attempters.
Adult↗
Homicide, suicide and CSF 5-HIAA.
Concentrations of 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 4-hydroxy-3-methoxyphenyl glycol (HMPG) in lumbar spinal fluid were measured by mass fragmentography in 16 men convicted for criminal homicide, 22 men who had attempted suicide, and 39 healthy male control subjects. Those men who had killed a sexual partner, and those who had attempted suicide, had lower levels of the serotonin metabolite, 5-HIAA in spinal fluid than the controls. It is suggested that low levels of 5-HIAA in spinal fluid reflect a disorder of serotonin turnover, which makes the individual more prone to acts of violence in states of emotional turmoil.
Adult↗